Endoscopic Ultrasound and Pancreatic Tumors





Key Points





  • Endoscopic ultrasound (EUS) is the most sensitive imaging modality for the diagnosis of pancreatic ductal adenocarcinoma, especially lesions less than 2 cm in size.



  • EUS is also the most sensitive imaging modality for the detection of pancreatic neuroendocrine tumors (PNETs) and is superior to both computed tomography (CT) and magnetic resonance imaging (MRI).



  • CT is the most accurate modality for the determination of tumor staging and assessment of resectability with exception of detecting portal vein invasion and small-volume ascites, where EUS may be superior. Detection of small hepatic metastases may also be more accurate with MRI and EUS.



  • EUS-guided fine-needle aspiration (EUS FNA) is the gold standard for tissue acquisition in pancreatic mass lesions. Diagnostic yield can be optimized by use of the fanning technique and presence of a cytopathologist to render an on-site diagnosis. Diagnostic yield can also be maximized by the use of recently available core biopsy needles in centers without on-site cytopathology support.





Examination Checklist for Evaluation of a Suspected Pancreatic Tumor


Tumor


The following characteristics of all visualized masses should be noted: maximal dimensions, irregular or well-defined borders, echogenicity, associated cystic structures, and the presence of pancreatic duct dilation.


Vascular Invasion


For tumors in the pancreatic head, their relationship to the portal vein, portosplenic confluence, superior mesenteric vessels, hepatic artery, and gastroduodenal artery should be noted. For tumors in the pancreatic body, their relationship to the celiac artery, superior mesenteric artery (SMA), portal confluence, hepatic artery, and splenic vessels should be defined. For tumors in the pancreatic tail, the splenic vessels should also be interrogated. The relationship between the tumor and the vessels should be carefully examined. Notation may be stated as follows: intact hyperechoic tumor/vessel interface, adherent to vessel wall without irregular interface, irregular tumor/vessel interface, tumor invasion, or occlusion of the vessel. For occlusion of the portal or superior mesenteric vein (SMV), venous collaterals in the liver hilum or periduodenal region may be seen. For splenic vein occlusion, collaterals in the splenic hilum or gastric fundus may occur.


Lymph Nodes


The following stations should be examined for possible metastatic disease: celiac axis, peripancreatic region (including head, body, and tail), porta hepatis, gastrohepatic ligament, aortocaval, and possibly posterior mediastinal stations. Metastatic lymph nodes will usually be round, well defined, hypoechoic, and at least 5 mm in diameter. However, not all malignant lymph nodes will have all of these features. If a suspected lymph node is identified, its characteristics and distance from the tumor should be noted. EUS FNA should be performed on suspected distant metastatic lymph nodes.


Liver


Transgastric and limited transduodenal examination of the liver should be examined for metastatic lesions. Liver metastases from primary pancreatic cancer are usually hypoechoic and well defined. One or more than one lesion may be identified. EUS FNA of any suspected lesion should be performed when accessible.


Ascites


This usually appears as a triangular or irregularly shaped anechoic region just outside the duodenal or gastric wall. It may be seen from peritoneal metastases or chronic venous occlusion. Omental nodules may also be visualized. EUS-guided fluid aspiration or biopsy of a nodule should be performed when possible.


Endoscopic Ultrasound-Guided Tissue Acquisition


Tissue sampling should be performed from the most distant metastatic site first. If ascites, a distant metastatic lymph node, omental nodule, or a suspicious liver lesion is present, one of these lesions should be sampled first. If these test negative for malignancy, either the suspected tumor or a regional lymph node may be sampled. The following information should be noted from each site biopsied: number of passes required, route of tissue acquisition, whether suction was used, and results of any onsite evaluation.


Staging


All suspected malignant tumors of the pancreas should be identified in terms of tumor-node-metastasis (TNM) staging based on the most current American Joint Committee on Cancer (AJCC) staging classification.




Pancreatic Ductal Adenocarcinoma


Background


Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related death in the United States, with 43,000 deaths per year and a dismal overall 5-year survival rate of only 8%. Early diagnosis and management planning are therefore essential for optimal clinical outcomes in these patients, as survival is largely dependent on cancer stage, with 5-year survival rate of 29% for localized disease compared with only 3% for metastatic disease. EUS combined with FNA is the most accurate modality available for the diagnosis of pancreatic cancer and has thus resulted in a paradigm shift in the management of these patients.


Detection of Pancreatic Ductal Adenocarcinoma


Endoscopic Ultrasound Versus Computed Tomography


EUS is a very sensitive modality for detecting pancreatic cancer, with a sensitivity of 89% to 100%, specificity of 50% to 100%, and accuracy of 94% to 96%. EUS has a high negative predictive value of 100%, with two studies showing that when patients with suspected pancreatic cancer had a normal EUS examination, pancreatic cancer was not diagnosed in any of them on long-term follow-up. Therefore a normal-appearing pancreas on EUS examination can reliably exclude pancreatic cancer.


Pancreatic cancer is seen as a hypoatteunating mass on CT in the majority of cases, although it can be isoattenuating in 10% of patients, in which case it is more difficult to visualize. The optimal type of CT imaging in patients with suspected pancreatic cancer is a contrast-enhanced, multiphasic (arterial phase to assess arterial involvement, pancreatic phase to visualize the mass, and portal venous phase to assess involvement of the portal vein and SMV) multidetector CT with minimal slice size of 5 mm, which has sensitivity of 70% to 100%. Helical CTs appear to have lower sensitivity (63% to 77%) than multidetector CTs for detecting pancreatic tumors. Also, the diagnostic sensitivity of CTs for detecting small pancreatic tumors less than 2 cm in size is only 77%.


Studies comparing CT with EUS for the detection of pancreatic cancer have shown equivocal results. Although older studies demonstrate superiority of EUS over helical CT, more recent studies show EUS to be either marginally superior or only comparable to multidetector CTs. Nevertheless, EUS appears to have a clear advantage over CT in two specific scenarios. First, studies have shown that EUS is superior to multidetector CT for the identification of small pancreatic mass lesions less than 2 cm in size ( Fig. 14.1A–C ). This is probably because small pancreatic mass lesions are more likely to be isoattenuating rather than hypoatteunating on CT and hence must be diagnosed by identifying secondary signs of pancreatic cancer, such as cutoff of the pancreatic duct, pancreatic duct dilation, atrophy of the pancreatic parenchyma, or absence of normal pancreatic contour. Second, EUS can diagnose pancreatic cancer in patients without a distinct mass lesion on CT but with a high clinical suspicion with a sensitivity of 68% to 97%, specificity of 43% to 71%, and accuracy of 72% to 92%. Therefore EUS should be performed in CT-negative patients in whom the clinical suspicion for pancreatic cancer remains high.




Fig. 14.1


Computed tomography of a patient who presented with obstructive jaundice but no definitive mass on imaging (A). Linear endoscopic ultrasound imaging revealed a 2-cm pancreatic head mass (B) that on rapid onsite evaluation (ROSE) was proven to be an adenocarcinoma (C) (Diff-Quik staining 200×). CB, Common bile duct; PV, portal vein.


Endoscopic Ultrasound Versus Magnetic Resonance Imaging


MRI can provide detailed imaging of the pancreatic parenchyma and pancreatic duct and has a sensitivity of 78% to 100% and an accuracy of 79% to 91% for detecting pancreatic tumors. In studies that compared EUS with MRI for the diagnosis of pancreatic cancer, EUS was at least equivalent or superior to MRI for visualizing pancreatic cancer. In one study of 62 patients, MRI had the lowest accuracy for tumor detection at 62% when compared with both EUS (63%) and CT (73%).


Contrast-Enhanced Endoscopic Ultrasound


Pancreatic adenocarcinoma is visualized as a hypoenhancing lesion on CE EUS, whereas chronic pancreatitis is either isoenhancing or hyperenhancing. In a meta-analysis of 1139 patients, contrast-enhanced EUS was shown to have a high sensitivity for diagnosing pancreatic cancer, with a pooled sensitivity of 94% and specificity of 89%. When compared with conventional EUS for performing FNA, although there was no significant difference in diagnostic performance between modalities, fewer passes were required to obtain a diagnostically adequate sample with contrast enhancement. A sufficient sample was obtained with just one pass in 60% of patients compared with only 20% with conventional EUS FNA. Therefore contrast-enhanced harmonic EUS appears to have a supportive role in the EUS FNA evaluation of pancreatic mass lesions and may be useful in identifying the optimal site for FNA, especially in patients with underlying chronic pancreatitis.


Endoscopic Ultrasound Elastography


EUS elastography utilizes the difference in tissue elasticity to distinguish between malignant and benign lesions. EUS elastography can produce either a qualitative assessment with generation of different color hues or a quantitative assessment with strain ratios. Several meta-analyses have been published on this imaging technique, with a sensitivity of 95% to 98% and a specificity of 67% to 76% for diagnosing pancreatic cancer.


Assessment of Resectability and Cancer Staging


Surgical resection is the only currently available treatment with potential for cure in patients with pancreatic cancer. Even though the 5-year survival remains poor at 10% to 20% postresection, survival has been shown to be significantly longer in patients undergoing margin-negative (R0) resection compared with nonsurgical candidates (14 vs. 5 months, P < .0001). Therefore accurate and timely pancreatic cancer diagnosis and staging are paramount in order to expedite referral to surgery.


Staging


Pancreatic cancer staging as determined by the AJCC (currently in its eighth edition) comprises the conventional TNM staging system: tumor characteristics (T), nodal involvement (N), and presence of metastatic lesions (M) ( Table 14.1 ). Patients with nodal involvement beyond the field of resection or metastatic disease are automatically deemed unresectable ; however, in patients with localized disease, resectable pancreatic cancer is defined as tumor without involvement of the surrounding major arteries, namely the celiac artery, SMA, and common hepatic artery (CHA). In addition, there is a lack of uniform consensus on the determination of suitability for resection in patients with venous involvement but without arterial involvement, with National Comprehensive Cancer Network (NCCN) and Alliance guidelines advocating surgical resection if the tumor has ≤180 degrees of contact with the portal vein or SMV. The definitions of resectability according to the NCCN guidelines are outlined in Table 14.2 .



TABLE 14.1

American Joint Committee on Cancer Eighth Edition for Pancreatic Cancer Staging

Taken from Amin MB, Edge SB, Greene FL, et al., eds. AJCC Cancer Staging Manual . 8th ed. New York: Springer; 2017.















































Tumor (T) Lymph Nodes (N) Metastases (M)
T1: Tumor size ≤2 cm N0: No lymph node involvement M0: No metastasis
T2: Tumor size 2–4 cm N1: 1–3 lymph node involvement M1: Metastasis present
T3: Tumor size >4 cm N2: ≥4 lymph node involvement
T4: Invasion of celiac artery or SMA
Staging
Stage 1 Stage 1A: T1, N0, M0
Stage 1B: T2, N0, M0
Stage 2 Stage 2A: T3, N0, M0
Stage 2B: T1–3, N1, M0
Stage 3 Any T, N2, M0
or T4, Any N, M0
Stage 4 Any T, Any N, M1

SMA, Superior mesenteric artery.


TABLE 14.2

The National Comprehensive Cancer Network Definitions of Tumor Resectability in Pancreatic Ductal Adenocarcinoma

Taken from Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Canc Netw . 2014;12:1083–1093.













































Resectable No distant metastases
Clear fat planes around celiac artery, hepatic artery, SMA
No SMV, PV distortion
Borderline resectable No distant metastases
Involvement of SMV or PV but with suitable vessel proximally and distally to allow safe resection
Gastroduodenal artery encasement up to hepatic artery with short segment encasement or direct abutment of hepatic artery without extension into the celiac axis
Tumor abutment of SMA ≤180 degrees of circumference of vessel wall
Unresectable Distant metastases
Metastases to LNs beyond field of resection
SMA encasement >180 degrees
Any celiac abutment for pancreatic head tumor
Celiac encasement >180 degrees for pancreatic body/tail tumor
Unreconstructable SMV or PV occlusion
Invasion/encasement of aorta or IVC

IVC, Inferior vena cava; LN, lymph nodes; PV, portal vein; SMA, superior mesenteric artery; SMV, superior mesenteric vein.


Tumor Classification and Local Vascular Invasion


Tumor size in conjunction with determination of celiac artery/SMA involvement constitute tumor classification in pancreatic ductal adenocarcinoma according to the AJCC criteria. CT is an accurate modality for assessing tumor classification and vascular involvement for the determination of resectability. The reported performance of CT in the evaluation of vascular invasion is varied, with a reported sensitivity of 56% to 85% and specificity of 82 to 100%. In a meta-analysis of 18 studies that assessed the diagnostic performance of CT for the assessment of vascular invasion, the pooled sensitivity and specificity were 77% and 81%, respectively. However, the sensitivity and specificity were both higher at 85% and 82%, respectively, when only five studies published from 2004 to 2008 were included. CT had a higher specificity for the assessment of arterial invasion compared with venous invasion (92% vs. 84%); however, the sensitivity was lower for arterial invasion (68% vs. 75%). Additionally, the pooled sensitivity and specificity were higher when CT with vascular reconstruction was performed: 84% and 85%, respectively, compared with 62% and 77% when vascular reconstruction was not performed.


EUS is an accurate modality for determining tumor size and yielding tissue diagnosis when used in conjunction with FNA. Also, EUS is considered to be an accurate modality for assessing portal vein invasion due to the ease of visualization from the duodenal bulb, with a reported sensitivity of 75% and specificity of 77% ( Fig. 14.2A and B ). In one comparative study, the overall accuracy of tumor staging was higher with EUS than with CT at 67% and 41%, respectively ( P < .001). This was corroborated by a systematic review of 11 studies that found EUS to be more accurate than CT for tumor staging.




Fig. 14.2


Linear endoscopic ultrasound imaging of the pancreatic head reveals a hypoechoic mass invading the portal vein (A). Invasion of the inferior vena cava is observed in another patient with pancreatic adenocarcinoma of the uncinate process (B). IVC, Inferior vena cava; PV, portal vein; SMA, superior mesenteric artery.


Nodal Classification.


Locoregional lymph nodes visible on EUS are located in the following stations and should be assessed when possible in all patients with suspected or FNA-proven pancreatic cancer: celiac axis, peripancreatic station, porta hepatis, gastrohepatic ligament, and aortocaval stations. On EUS examination, metastatic lymph nodes appear round and hypoechoic; they are more than 1 cm in size and have well-defined margins. When all four of these features are seen, the likelihood that the lymph node in question is malignant is 80% to 100%.


Overall, studies have shown that CT and EUS have similar operating characteristics for the assessment of lymph node involvement in pancreatic cancer, with sensitivities of 33% to 69% and 36% to 44%, respectively. In one prospective observational study of 120 patients with known pancreatic cancer, accuracy for nodal staging was comparable between EUS and CT at 44% and 47%, respectively. In a systematic review that included eight studies, the accuracy for nodal staging in five studies was found to be greater for EUS than CT. However, three recent studies did not demonstrate any such difference between CT and EUS.


Presence of Distant Metastases.


Owing to the inherent limitations of EUS in the assessment of structures distant to the transducer, CT was found to be superior to EUS for detecting metastatic disease, with an accuracy of 88%. There are nevertheless two caveats to this rule. First, small hepatic metastases can be missed on CT, and both EUS and MRI appear to have an advantage over CT in these patients ( Video 14.1 ). One must be mindful of the fact that EUS may be limited in the assessment of the entire liver parenchyma, as the right lobe of the liver is often not well visualized on EUS ( Fig. 14.3A–C ). In one study of 100 patients with pancreatic cancer, the sensitivity for detecting liver metastases was significantly higher with MRI, at 85%, compared with 69% for CT ( P = .046), although no significant difference was seen between the two modalities for detection of the primary tumor. This was supported by a smaller prospective study of 31 patients, where the sensitivity and specificity for liver metastases were higher with MRI than with CT (86.7% and 97.5% for MRI vs. 53.3% and 77.8% for CT). Second, CT is poor at assessing peritoneal metastases, which manifest as ascites and peritoneal nodules. In particular, small-volume ascites, which may not yet be detectable on CT, can be visualized and aspirated for cytology during EUS. In one study of 85 patients with ascites present on EUS, it was not seen on CT in 82%. Subsequent EUS FNA of the ascitic fluid in 31 of these patients, resulted in a diagnosis of malignant ascites in 16% and thereby altered the treatment plan ( Fig. 14.4 ).




Fig. 14.3


Linear endoscopic ultrasound (EUS) imaging of the left lobe of the liver demonstrates hypoechoic lesions in a patient with metastatic pancreatic cancer (A). Fine-needle aspiration using a 22-gauge needle revealed adenocarcinoma (B) (Diff-Quik staining 200×). Hepatic metastases can also appear as hyperechoic lesions on EUS (C).



Fig. 14.4


Peritoneal carcinomatosis manifesting as ascites in a patient with stage IV pancreatic cancer.


Video 14.1


Endoscopic Ultrasound-Guided Fine-Needle Aspiration of a Hypoechoic Mass in the Left Lobe of the Liver Reveals Metastatic Pancreatic Adenocarcinoma



Tumor Resectability.


Studies have shown helical CTs to be accurate for determining resectability, with a positive predictive value of 45% to 87% for accurately predicting resectability and positive predictive value of 89% to 100% for assessing unresectability. Contrast-enhanced multiphasic multidetector CT is the current CT imaging modality of choice for tumor staging and the assessment of local resectability. In a study of 79 patients with pancreatic ductal adenocarcinoma who underwent multidetector CT prior to surgical resection, the sensitivity, specificity, and accuracy for resectability were 100%, 71%, and 89%, respectively.


In comparing the different diagnostic modalities for the assessment of vascular invasion and resectability, studies comparing CT with EUS have yielded variable results. In a study of 62 patients with pancreatic cancer, CT had the highest sensitivity and accuracy for determining locoregional extension (66% and 74%, respectively) and vascular invasion (67% and 83%, respectively), followed by MRI (accuracy of 68% for locoregional extension, 74% for vascular invasion) and then EUS (accuracy of 62% for locoregional extension, 76% for vascular invasion). In the assessment of tumor resectability, CT had the highest accuracy at 83%, compared with 75% for MRI and 67% for EUS. However, in a more recent study of 86 patients, EUS was superior to CT for the evaluation of resectability at 83% compared with 60%.


Endoscopic Ultrasound-Guided Fine-Needle Aspiration


EUS FNA of pancreatic mass lesions has a pooled sensitivity of 85% to 89% and specificity of 96% to 98% ; it is the recommended first-line modality for tissue acquisition in patients with suspected pancreatic malignancy. EUS FNA of pancreatic mass lesions is, however, considered the most challenging of all EUS FNAs; therefore the use of correct techniques, accessories, and on-site cytopathology evaluation when available are critical to maximize the diagnostic yield.


Fine-Needle Aspiration Techniques/Accessories for Tissue Acquisition


Needle Size.


FNA needles are available in three sizes: 19 gauge, 22 gauge, and 25 gauge. Because of the stiffness associated with traditional 19-gauge needles, especially when the echoendoscope is placed in a torqued position for transduodenal passes, 22- and 25-gauge needles are most frequently utilized for performing EUS FNA. There have been conflicting data regarding the performance of the 22- compared with the 25-gauge needle for EUS FNA of pancreatic masses. In a meta-analysis of eight comparative studies, the pooled sensitivity of the 25-gauge needle was significantly higher than that of the 22-gauge needle (93% vs. 85%), with no significant difference in the specificity (100% for the 22-gauge needle vs. 97% for the 25-gauge needle). However, in three randomized trials, similar performance was observed between the 22-gauge and the 25-gauge needles, with no significant difference between the two needle types for diagnostic adequacy, number of passes required for diagnosis, and adverse event rates. Furthermore, in a recently completed randomized trial of 352 patients with pancreatic masses, the operating characteristics of EUS FNA were comparable between the 22- and 25-gauge needles. Therefore needle size alone does not appear to have a significant impact on the success of EUS FNA of pancreatic masses and, overall, both 22- and 25-gauge needles appear to perform equally well.


Route of Fine-Needle Aspiration.


EUS FNA of pancreatic masses located in the body and tail is performed via the transgastric route, whereas the transduodenal route is utilized for pancreatic head and uncinate lesions. For transduodenal FNAs, the torqued echoendoscope position and acute angulation of the scope tip can result in difficulty in pushing the stiffer 22-gauge needle out of the scope. In a two-phase study of over 1000 patients, an algorithmic approach to EUS FNA was undertaken, with use of 22-gauge needles for transgastric FNAs and 25-gauge needles for transduodenal FNAs. The result was a significant reduction in the technical failure rate from 10.9% to 1.8% ( P < 0.001), with a significantly lower needle cost per procedure.


Fanning.


The fanning technique describes moving the FNA needle in multiple areas within the lesion during FNA rather than sampling just one area of the mass, as occurs with the standard technique. In the only randomized trial that compared the standard and fanning techniques for EUS FNA of pancreatic masses, the use of the fanning technique (four to-and-fro movements in each of the four areas sampled within the lesion) was associated with a significantly lower number of passes required for diagnosis. In addition, there was a trend toward higher diagnostic accuracy with the fanning technique at 96% versus 77%, although the difference was not statistically significant. The fanning technique should therefore be used when possible for EUS FNA of pancreatic mass lesions.


Suction.


The current published literature on the benefit of using suction for EUS FNA of pancreatic mass lesions is both scant and equivocal. In a small randomized trial, sensitivity and accuracy were both significantly higher in the suction group, with another second randomized trial showing just a trend toward higher sensitivity in the suction group. However, in a recently completed four-arm randomized trial of 352 patients comparing the use of 22- and 25-gauge needles with and without suction in patients with solid pancreatic mass lesions, no significant difference in the operating characteristics of EUS FNA was seen between the four groups. However the use of suction with the 22-gauge needle was associated with increased specimen bloodiness and an increased number of passes for onsite diagnosis.


Stylet.


There appears to be no significant advantage to using a stylet in EUS FNA of pancreatic mass lesions, with studies showing that using a stylet is not associated with a significant improvement in diagnostic adequacy, sensitivity, specificity, or accuracy. Therefore, for convenience, because the stylet is already in situ when the needle is first opened, the stylet can remain in situ for the first pass and then be discarded for subsequent passes.


Specimen Interpretation and Processing


The availability of a cytopathologist to render an on-site diagnosis is an extremely important determinant of diagnostic accuracy in EUS FNA of pancreatic mass lesions. In a meta-analysis of 3644 patients, the presence of an on-site cytopathologist was the only determinant of an accurate diagnosis following EUS FNA of pancreatic masses.


However, owing to financial constraints, on-site cytopathologic evaluation is not universally available. In such cases, the aspirate can be placed in a preservative for specimen processing and off-site assessment at a later time. However, standard FNA needles may not be optimal for this purpose. In one randomized trial evaluating the 25-gauge needle for its ability to acquire diagnostic core tissue for off-site assessment (cell block), diagnostic adequacy was only 81% regardless of the number of dedicated passes performed. This is important to bear in mind in centers without on-site cytopathology support that rely solely on off-site evaluation of FNA samples, as the acquired sample may be nondiagnostic in up to 20% of cases.


Challenges in Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Mass Lesions


Uncinate Mass Lesions.


Pancreatic masses located in the uncinate process are the most challenging lesions for EUS FNA. This is because uncinate masses usually require FNA from the second portion of the duodenum, where acute angulation of the echoendoscope can prevent easy passage of the needle into the mass. Needle passage into the mass can be aided in this situation by shortening the echoendoscope so that it is in a relatively straight position in the second portion of the duodenum; however, this position can, in turn, be unstable, causing the echoendoscope to fall back into the stomach during FNA. Transduodenal FNAs are therefore easier with the thinner caliber and more flexible 25-gauge needles as opposed to the stiffer 22- or 19-gauge needles. The adoption of an algorithmic approach to EUS FNA—whereby 25-gauge needles are used for transduodenal FNA of the pancreatic head and uncinate masses and 22-gauge needles are used for transgastric FNA of pancreatic body and tail masses—resulted in a significant decrease in the rate of technical failure ( Fig. 14.5A and B ; Video 14.2 ).




Fig. 14.5


Endoscopic ultrasound-guided fine-needle aspiration of a pancreatic uncinate mass (A) ( arrow points to the FNA needle); note the perpendicular direction in which the lesion was sampled from the second portion of the duodenum on fluoroscopic view (B).


Video 14.2


Endoscopic Ultrasound-Guided Fine-Needle Aspiration of a Pancreatic Uncinate Mass Using a 25-Gauge Needle


The fluoroscopic image reveals technical challenges associated with sampling of pancreatic uncinate masses.



Chronic Pancreatitis.


EUS FNA of pancreatic mass lesions is more challenging in patients with underlying chronic pancreatitis, in whom the mass can be more difficult to identify owing to the presence of coexisting lobulations and calcifications. Also, the interpretation of cytologic specimens can be more challenging because the inflammatory cells can mimic or obscure malignant cells. Additionally, the aspirates are frequently acellular, resulting in an inadequate or nondiagnostic sample. Two studies have shown low sensitivity of 54% and 74% for diagnosing pancreatic cancer in the setting of chronic pancreatitis. Therefore, if clinical suspicion is high—given the high rates of false-negative diagnosis in patients with pancreatic cancer and underlying chronic pancreatitis—EUS FNA should be repeated to conclusively exclude a diagnosis of malignancy ( Fig. 14.6A–D ).




Fig. 14.6


Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of a pancreatic uncinate mass in the setting of chronic pancreatitis (A). Note the ill-defined uncinate mass, which is difficult to differentiate from the surrounding pancreatic parenchyma. Rapid onsite evaluation (ROSE) revealed ductal adenocarcinoma in the setting of desmoplastic fibrosis (B; Diff-Quik staining, 200×). In another patient with chronic pancreatitis, the pancreatic head mass was notable as an area of blue hue on EUS elastography (C), which was used to target for EUS FNA. ROSE revealed ductal adenocarcinoma (D; Diff-Quik staining, 400×).


Adverse Events of Fine-Needle Aspiration


EUS FNA of pancreatic mass lesions is generally safe. In a meta-analysis of 10,941 patients, the reported overall adverse event rate was 1%. The type of adverse events encountered include acute pancreatitis (0.44%), abdominal pain (0.38%), bleeding (0.1%), fever (0.08%), and infection (0.02%). The rate of tumor seeding following EUS FNA is reported at 2%, which is significantly lower than that observed with percutaneous CT-guided biopsy (16.3%; P < .025). Furthermore, the majority of adverse events appear to occur within 1 week of the procedure. In a prospective study of 158 patients who underwent EUS FNA of pancreatic mass lesions, adverse events occurred in 10 patients periprocedurally or immediately after the procedure, followed by adverse events in another 20 patients within 72 hours of the procedure. At 30-day follow-up, no other adverse events had been reported in the interim. The overall rate of major adverse events in this study was 2.5%.


Fine-Needle Biopsy


Specially designed FNB needles have been developed to obtain histologic core tissue during EUS-guided tissue sampling; these samples have several theoretical advantages over traditional FNA samples. One, due to their retained architecture, histologic core tissue specimens are easier to interpret than cytologic specimens obtained via EUS FNA. Two, histologic core tissue enables ancillary testing, especially in patients with challenging lesions such as metastatic cancers, gastrointestinal stromal cell tumors, and lymphomas. Three, core tissue samples are more conducive to performing molecular profiling and delivering personalized anticancer therapy.


Studies have shown varied success with FNB needles. In one meta-analysis there was no significant difference in the performance of the reverse-bevel-tip FNB needle (ProCore, Cook Endoscopy, Winston-Salem, North Carolina) as compared with standard FNA needles for EUS-guided sampling of solid lesions, including diagnostic adequacy, diagnostic accuracy, and procurement of histologic core tissue. However, preliminary data suggest that the fork-tip (SharkCore, Medtronic Corp., Boston, Massachusetts) and Franseen (Acquire, Boston Scientific Corp., Natick, Massachusetts) needles yield better histologic tissue. In a case-control study of 156 patients, histologic tissue was procured in a significantly higher proportion of patients using the fork-tip needle (95 vs. 59%, P = .001), after performing a significantly lower number of passes (median 2 vs. 4 passes, 0.01). In a series of 30 patients, the Franseen needle was able to obtain a diagnostic cell block in 96.7% of patients, which is significantly higher than that previously reported ( Fig. 14.7A and B and Fig. 14.8A and B ; Video 14.3 ). Also, successful ancillary testing was possible in all patients with gastrointestinal stromal tumors (GISTs), PNETs, and metastatic cancer. In the first randomized trial to date comparing FNA with FNB needles (Acquire, Boston Scientific Corp.) for EUS-guided sampling of pancreatic masses, EUS FNB was associated with a significantly higher rate of diagnostic cell block (97.8 vs. 82.6%, P = .03) and was able to procure significantly greater amount of tissue, tumor cells, and desmoplastic fibrosis.


Feb 19, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on Endoscopic Ultrasound and Pancreatic Tumors

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